Can tiotropium add-on inhalation revolutionize therapy in elderly asthmatic patients? A treatable traits approach towards successful aging.

We are in the era of rapid aging of the global population. Elderly asthmatic patients have an increased frequency of hospitalization and a high mortality rate. In this review, we focus on comorbidities and treatment issues in terms of the predictors of asthma control in the elderly. Some frequent comorbidities, such as chronic obstructive pulmonary disease, chronic sinusitis, obesity, and depression, are associated with uncontrolled asthma in elderly asthmatic patients. Smoking status in elderly asthmatic patients was associated with more frequent exacerbations. Management of comorbidities should be taken into account when we treat elderly asthmatic patients. Low treatment adherence, which is common in elderly asthmatic patients, predicts poor asthma control status. A poor knowledge about asthma, cognitive function impairment, and inappropriate inhaler technique result in low treatment adherence. Polypharmacy is associated with low treatment adherence, adverse drug reactions, and drug-drug interactions, and it is supposed to be a predictor of asthma control. Multifactorial assessments, including comorbidities, treatment adherence, and polypharmacy, are important for better asthma control in elderly asthmatic patients. Further studies on the strategy for the management of elderly asthmatic patients in a real-world setting are warranted.

PurposeThe ‘treatable traits’ strategy for patients with chronic inflammatory airway diseases, especially asthma and chronic obstructive pulmonary disease (COPD), is a focus of interest, because it implements precision and personalized medicine. Asthma-COPD overlap (ACO), a phenotype involving both asthma and COPD, is an important disease entity because patients with ACO have significantly worse outcomes, conferring greater economical and social burdens. Some guidelines for ACO recommend add-on therapy of long-acting muscarinic antagonists to inhaled corticosteroids and long-acting β2 agonists. However, this approach is based on extrapolation from patients with asthma or COPD alone. Consequently, a ‘treatable traits’ approach suitable for ACO remains obscure.MethodsA 12-week open-label cross-over pilot study was conducted in patients with ACO to investigate the effect of tiotropium bromide (TIO) 5 µg/day add-on therapy to fluticasone propionate/formoterol fumarate (FP/FM) 500/20 µg/day compared with FP/FM 500/20 µg/day alone. A 4-week run-in period and two 4-week treatment periods were included.ResultsA total of 18 male patients with stable ACO participated in this pilot study. All patients were ex-smokers. Mean values ± standard deviation (SD) for forced expiratory volume in 1 second (FEV1) were 1.21 ± 0.49 L after the run-in period, 1.20 ± 0.51 L after the FP/FM combination therapy period, and 1.30 ± 0.48 L after the TIO add-on therapy to FP/FM period. FEV1 values after the TIO add-on therapy FP/FM period were significantly higher than those after the run-in period (p < 0.01).ConclusionTIO add-on therapy to FP/FM in patients with ACO, considered difficult to treat because of the presence of both asthma and COPD, resulted in improvements in lung function parameters in this real-world pilot study, indicating the potential value of TIO add-on therapy as a “treatable traits” option for standard treatment for ACO.

Differences in medication compliance among elderly patients with asthma in Chicago

There are many well-defined risk factors for fatal asthma exacerbation; however, few data exist about the link between the severity of asthma and severity of exacerbation. The aim of this study was to determine if there is any patient and disease-related factor that predicts the severity of asthma exacerbation. The retrospective data of asthmatic patients followed up in our clinic were analyzed. Asthmatic patients who had at least one exacerbation were included. Patient and disease characteristics, comorbidities, and compliance were evaluated. We analyzed 335 asthma exacerbations of 189 asthmatic patients. Eighteen patients had intermittent asthma, 115 patients had mild persistent asthma, 45 patients had moderate persistent asthma, and 11 patients had severe persistent asthma. Of the 189 asthmatic patients 8.1% of the exacerbations were mild, 52.5% were moderate, and 39.4% were severe. There was a significant correlation between the severity of asthma and severity of exacerbation (r = 0.32; p < 0.001). When elderly (> or =60 years old) and younger (<60 years old) asthmatic patients were compared, elderly asthmatic patients had severe asthma exacerbation significantly at a higher rate than younger asthmatic patients (severe asthma exacerbation rates are 67.3 and 33.9% in elderly patients and younger asthmatic patients, respectively; p < 0.001). A significant correlation was found between the severity of exacerbation and age (r = 0.25; p < 0.001). Among the other patient and disease-related factors, asthma severity and older age were the only significant factors that contributed to the severity of exacerbation. These data show that older age as a patient-related factor and worse asthma severity as a disease-related factor could contribute to exacerbation severity in asthmatic patients.

Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma

Objective To evaluate the efficacy and safety of long-term nebulized corticosteroids and inhaled bronchodilators therapy on asthma in long-term poor controlled elderly patients. Methods Prospective, randomized control study was conducted. 63 elderly asthma patients, who received inhaled corticosteroids or combined with other long-term medication treatment for asthma control for more than 3 months but were still in moderate to severe persistent asthma state, were randomly divided into nebulizer treatment group (n=31) and dry powder inhalation group (n=32), and they were treated correspondingly with Budesonide inhalation suspension 1 mg and Salbutamol 2.5 mg BidorBudesonide/Formoterol powder 320/9 μg inhalation Bid. Patients in the two groups were evaluated for the differences in lung function, acute exacerbations of asthma, asthma control test (ACT) and adverse effects after 12-week treatment. Results The improvement in morning peak expiratory flow (PEF) and ACT score were better in the test group than in the control group 〔(29.2±14.4) ml vs. (15.8±13.5) ml, (4.8±2.2) vs. (3.0±2.7), t=3.715 and 2.897, P=0.000 and 0.005〕, but there were no statistical differences in average daily use of relievers and severe acute exacerbations between the test and control groups (t=-1.512, P=0.136; χ2=2.238, P=0.135). The local adverse effects caused by inhaled corticosteroids had no significant difference between the two groups. Conclusions Compared with the powder inhalation, the nebulizer inhalation administration of corticosteroids and bronchodilators could improve the asthma symptoms and lung function better in elderly patients with serious asthma condition and shows a good safety in the 12 weeks of continuous treatment. Key words: Asthma; Glucorticosteroids; Metered dose inhalers

Atopy Is Associated with Age at Asthma Onset in Elderly Patients

Background Biologics are the important drugs for severe asthma, but clinical trials included few elderly patients. Data on the safety and efficacy of benralizumab in elderly asthma patients are limited. Methods This clinical study was a multicentre, retrospective, observational study at two hospitals. Patients aged ≥18 years diagnosed with severe asthma treated with benralizumab were included. Elderly patients were defined as those aged 70 years or older. Efficacy and safety were then analyzed in elderly and non-elderly patients. The primary endpoints were the annual number of asthma exacerbations for efficacy and the discontinuation rate due to adverse events for safety. Results Between August 2016 and October 2022, 61 patients were enrolled; 10 patients were excluded, and 51 (22 elderly, 29 non-elderly) patients were analyzed. In elderly patients, the annual number of asthma exacerbations before treatment with benralizumab (pre-benralizumab) was 3.78, and the number during treatment with benralizumab was 1.26, a decrease of 2.52 (95% confidence interval [CI], 1.3 to 3.74, p < 0.001). In non-elderly patients, the annual number of asthma exacerbation in the pre-benralizumab period was 3.24, and during treatment with benralizumab it was 0.68, a decrease of 2.56 (95% CI, 1.3 to 3.82, p < 0.001). There was no significant difference in discontinuation due to treatment-related adverse events (elderly vs non-elderly, 2 (9%) vs 0 (0%), p = 0.18). Conclusion Benralizumab reduced the annual number of asthma exacerbations and was well tolerated in elderly patients.

Background Because the mean lifespan is increasing and the percentage of elderly people among the population as a whole is also increasing, the management of elderly bronchial asthma patients will be an important issue in medicine in the future. In the present study, based on questionnaires given to 3224 asthmatic patients in Niigata Prefecture, the characteristics, management and circumstances of elderly asthmatic patients were investigated. Methods Questionnaires were completed by asthmatic patients and their physicians in participating institutions within Niigata Prefecture from September to October 1999. Patients more than 65 years of age were defined as elderly asthmatic patients and a comparison was made between these patients and younger asthmatic patients who were less than 64 years of age and were used as a control group. Results In the classification of bronchial asthma, a greater frequency of infectious and mixed-type bronchial asthma was found in the elderly, whereas the use of peak flow meters was lower in this group. Significant differences were found for both self- evaluation of the condition of the asthma and satisfaction with daily life between the two age groups. A lower incidence of ambulance use, emergency room visits and use of inhaled steroids was observed in elderly patients, although the incidence of hospitalization and use of oral steroids was higher. The discrepancy between objective and subjective evaluation of asthma control, the incidence of the use of both inhaled and oral steroids and the low use of peak flow meters were problematic in the elderly. Conclusions Based on sufficient consideration of the problems specifically related to elderly asthmatic patients, adequate education and careful management of asthma in this group are required, and the accumulation of these steps will result in the achievement of the guidelines final goals.

Asthma in elderly patients causes excessive suffering and inconvenience. Regimens with better efficacy and less adverse events are still in need of researches. To investigate the effect of montelukast sodium plus budesonide on lung function, inflammatory factors, and immune levels in elderly asthma patients. A total of 180 patients with asthma were assigned into the control group and the observation group. The control group was given aerosol inhalation of budesonide suspension, while the observation group was given budesonide inhalation and oral montelukast sodium. The treatment effect, lung function (forced expiratory volume in 1s (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF)%), inflammatory factors (interleukin (IL)-4, IL-6, and tumor necrosis factor-α (TNF-α)), and immune level (immunoglobulin (Ig) A, and IgE) were analyzed and compared between the two groups. After treatment, the effective rate was significantly higher in the observation group. The lung function and serum inflammatory factors were improved in both groups. The FEV1, FVC, and PEF% in the observation group were better, and the inflammatory factors IL-4, IL-6, and TNF-α were lower. Patients in both groups showed elevated IgA level and reduced IgE level, and the improvements were more significant in the observation group. There was no significant difference between the two groups in terms of adverse reaction. Montelukast sodium plus budesonide has a promising clinical effect on asthma in elderly patients, effectively improves lung function and immunocompetence, and controls inflammatory response, without increasing the adverse reaction.

Background: Fixed airway obstruction in asthma, which could be also called as asthma-chronic obstructive pulmonary disease (COPD) overlap, is associated with more morbidity and mortality burden, particularly in the elderly. However, risk factors for developing fixed airway obstruction are still under studied in elderly asthma patients. Objectives: We aimed to investigate risk factors of fixed airway obstruction among a group of elderly asthma patients. Methods: A total of 306 patients were included. Their lung function parameters during 3-year treatment period were collected, and fixed airway obstruction was defined if the best FEV1/FVC was less than 0.70 during the recent 1-year9s treatment period. Baseline parameters such as disease duration, smoking history, comorbidity, or serum IgE levels were analyzed for the associations with fixed airway obstruction. Results: The prevalence of fixed airway obstruction was 40.2% in our group of elderly asthma patients (mean age 71.3 years old). In univariate analyses, fixed airway obstruction was significantly associated with older age, male sex, smoking history, lower body mass index, and serum staphylococcal enterotoxin-specific IgE (SE-IgE) levels. In multiple logistic regression analyses, smoking history had the strong association with fixed airway obstruction. However, SE-IgE levels also had the significant relationships with fixed airway obstruction, independently of smoking history. Conclusions: Smoking history is a significant risk factor for fixed airway obstruction in elderly asthma. Our identification of SE-IgE sensitization as a potential risk factor for COPD overlap in elderly asthma warrants further investigation of its mechanism and clinical implication.

Factors associated with in-hospital complications and long-term implications of these complications in elderly patients undergoing endovascular aneurysm repair

BackgroundGiven effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the respiratory system and epidemiological burden of asthma worldwide, coronavirus disease 2019 (COVID-19) in asthma patients caused reasonable concern to be a “dangerous” combination in early pandemic. This is especially pertinent to elderly patients with asthma since older age, diabetes, cardiovascular disease, and hypertension, is associated with more serious complications of COVID-19 and higher mortality. Blood eosinopenia occurs as a part of the total cytopenia at the early stage of severe COVID-19 due to an effect of SARS-CoV-2 virus on the immunity and severe inflammation. Therefore, blood cell count monitoring could be useful for the diagnosis and outcome prediction in COVID-19. The aim of this study was to investigate a relationship between blood eosinophil count and outcomes of COVID-associated lung injury in elderly patients with asthma.MethodsThis was a prospective cohort study involving elderly patients with asthma (>60 years of age, n=131). All patients were admitted to a hospital for COVID-19 from October 1, 2020, to September 30, 2021. Those patients who completed their hospital treatment (were discharged or died) by December, 30, 2021, were enrolled in the study. All the patients were previously diagnosed with asthma according to Global Initiative for Asthma (GINA) criteria. The diagnosis of COVID-19 was confirmed by positive polymerase chain reaction (PCR) test, typical clinical symptoms, and radiological signs of multifocal pneumonia. Survived patients were followed up by weekly phone calls for 90 days after discharge. The complete blood count was measured in the whole blood samples obtained at admission. Hazard ratio was calculated using univariable and multivariable Cox proportional hazards regression models.ResultsIn total, 131 patients were enrolled in the study. Eighty-six patients survived, 30 patients died in the hospital, and 15 patients died post-discharge. Common independent predictors of death were the Charlson Comorbidity Index and eosinopenia. Survived patients had higher blood eosinophil count compared to patients who died in the hospital or post-discharge (P=0.001 and P=0.04, respectively). The cut-off eosinophil count was estimated as 100 cells/L; higher eosinophil count was seen in 24% of survivors and in none of non-survivors (P=0.002 and P=0.04, respectively). The absolute eosinophil count was a significant predictor of in-hospital death [odds ratio (OR), 0.64; 95% confidence interval (CI): 0.49–0.84; P=0.002] and death post-discharge (OR, 0.78; 95% CI: 0.65–0.95; P=0.01). Median survival, in-hospital and post-discharge, was shorter in patients with eosinophil count ≤100 cells/L (P<0.001 and P=0.04, respectively).ConclusionsBlood eosinophil count could be used as a prognostic marker of outcome in elderly patients with asthma and COVID-associated lung injury. Eosinophil level ≤100 cells/µL could be used as a threshold for predicting poor outcome, both in-hospital and 90-day post-discharge.

The proportion of elderly patients in North America is increasing. This has resulted in an increased number of elderly patients undergoing cosmetic procedures. The purpose of this study was to determine the incidence of postoperative complications in elderly patients (age ≥65) undergoing elective aesthetic plastic surgical procedures compared with younger patients. A total of 183,914 cosmetic surgical procedures were reviewed using the prospectively enrolled cohort of patients in the CosmetAssure database. Comorbidities and postoperative complications in elderly and younger patient groups were recorded and compared. A separate analysis of postoperative complications was performed in the octogenarian subgroup (age ≥80). A total of 6786 elderly patients who underwent cosmetic procedures were included in the study. Mean ages (±standard deviation) in elderly and younger patients were 69.1 ± 4.1 and 39.2 ± 12.5 years, respectively. The elderly patient population had more men, a higher mean body mass index (BMI), a higher prevalence of diabetes mellitus (DM), and fewer smokers compared with the younger patients. The overall postoperative complication rate was not significantly different between elderly and younger patients. When stratified by type of cosmetic procedure, only abdominoplasty was associated with a higher postoperative complication rate in elderly compared with younger patients. The most common postoperative complications in elderly patients were hematoma and infection. The overall postoperative complication rate in octogenarians was 2.2%, which was not significantly different from the younger population. Cosmetic procedures in elderly patients, including octogenarians, remain safe with an acceptable complication rate compared to younger patients.

Evaluation of patients’ real-world post-dispensing use and storage environments of tiotropium bromide Respimat® soft mist inhaler on its in vitro dose delivery and lung deposition